R-loop modulated epigenetic regulation in T helper cells mechanistically associates coronary artery disease and non-small cell lung cancer

Abstract

The effect of epigenetics in coronary artery disease and Non-small cell lung cancer (NSCLC) is presently developing as a significant vital participant at various levels from pathophysiology to therapeutics. We would like to find out the conjunction of some regular epigenetic regulations which decides the example of either acetylation/deacetylation or methylation/demethylation on various gene promoters associated with their pathogenesis. Expressions of some of the genes (e.g., VEGFA, AIMP1, etc.) are either up regulated or down regulated in a similar pattern where several DNA damage (e.g. H2A.X) and repair factors (e.g. BRCA1, RAD51, ERCC1, XPF), Transcription coupled DNA repair factor, Replication proteins are involved. Additionally, epigenetic changes, for example, histone methylation was found unusual in BRCA1 complex in CAD and in the NSCLC patients. Epigenetic therapies such as CRISPR/Cas9 mediated knockout/overexpression of specific gene (BRCA1) showed promising changes in diseased conditions, whereas it affected the R-loop formation which is vulnerable to DNA damage. Involvement of the common epigenetic mechanisms, their interactions and alterations observed in our study will contribute significantly in understanding the development of novel epigenetic therapies soon.

Keywords

• Epigenetics
• Histone methylation
• VEGFA
• AIMP1
• BRCA1
• R-loop